Synthesis of new analogs of AKBA and evaluation of their anti-inflammatory activities

Publication date: 15 February 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 4
Author(s): Bharani Meka, Suryachandra Rao Ravada, Muthyala Murali Krishna Kumar, Kurre Purna Nagasree, Trimurtulu Golakoti
A new series of 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid analogs (5, 7, 8, 10, 13, 18a-d, 27a-c, 28a-d) were synthesized by modification of hydroxyl and acid functional moieties of boswellic acids. The structures of these analogs were confirmed by spectral data analysis (¹H, ¹³C NMR and mass). Compounds 18b, 27a and 8 showed potent 5-lipoxygenase enzyme inhibitory activity (IC50: 19.53, 20.31 and 44.14μg/mL). The computational studies revealed that selectivity of AKBA is due to its fitment into the 5-LOX receptor, which is missing for the other enzymes like 12-LOX, COX-1 and COX-2. Our study found potentiating effects of 2-formyl and 3-keto substituents in reviving inactive AKBA analogues possessing essential COOH group at 4th position.

Graphical abstract

http://ift.tt/2l8Nw86

Mycobacterium tuberculosis chorismate mutase: A potential target for TB

Publication date: Available online 4 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Manjulatha Khanapur, Mallika Alvala, Maddela Prabhakar, K. Shiva Kumar, R.K. Edwin, P.S.V.K. Sri Saranya, Raj Kumar Patel, Gopalakrishnan Bulusu, P. Misra, Manojit Pal
Mycobacterium tuberculosis chorismate mutase (MtbCM) catalyzes the rearrangement of chorismate to prephenate in the shikimate biosynthetic pathway to form the essential amino acids, phenylalanine and tyrosine. Two genes encoding chorismate mutase have been identified in Mtb. The secretory form,∗MtbCM (encoded by Rv1885c) is assumed to play a key role in pathogenesis of tuberculosis. Also, the inhibition of MtbCM may hinder the supply of nutrients to the organism. Indeed, the existence of chorismate mutase (CM) in bacteria, fungi and higher plants but not in human and low sequence homology amongst known CM makes it an interesting target for the discovery of anti-tubercular agents. The present article mainly focuses on the recent developments in the structure, function and inhibition of MtbCM. The understanding of various aspects of MtbCM as presented in the current article may facilitate the design and subsequent chemical synthesis of new inhibitors against ∗MtbCM, that could lead to the discovery and development of novel and potent anti-tubercular agents in future.

Graphical abstract

http://ift.tt/2l8NwoG

Design, Synthesis and Biological Evaluation of 2,4-Disubstituted Oxazole Derivatives as Potential PDE4 Inhibitors

Publication date: Available online 3 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Ya-Sheng Li, De-Kun Hu, Dong-Sheng Zhao, Xing-Yu Liu, Hong-Wei Jin, Gao-Peng Song, Zi-Ning Cui, Lian-Hui Zhang
In this study, a series of pyrazole derivatives containing 4-phenyl-2-oxazole moiety were designed and synthesized in a concise way, some of which exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNF-α release. Compound 4c displayed the strongest inhibition activity (IC50 = 1.6±0.4 μM) and good selectivity against PDE4B. Meanwhile, compound 4c showed good in vivo activity in animal models of asthma/COPD and sepsis induced by LPS. The primary structure–activity relationship study showed the 3,5-dimethylpyrazole residue was essential for the bioactivity, and the substituted group R1 at the benzene ring also affected the activity. Docking results showed that compound 4c played a key role to form integral hydrogen bonds and a π-π stacking interaction, using hydrazide scaffold (-CO-N-N-) and pyrazole ring respectively, with PDE4B protein. While the rest part of the molecule extended into the catalytic domain to block the access of cAMP and formed the foundation for inhibition of PDE4B. Compound 4c would be great promise as a lead compound for further study based on the preliminary structure-activity relationship and molecular modeling studies.

Graphical abstract

http://ift.tt/2l8S2Uq

An epigenetic modifier induces production of (10′S)-verruculide B, an inhibitor of protein tyrosine phosphatases by Phoma sp. nov. LG0217, a fungal endophyte of Parkinsonia microphylla

Publication date: Available online 3 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Juliana R. Gubiani, E.M. Kithsiri Wijeratne, Taoda Shi, Angela R. Araujo, A. Elizabeth Arnold, Eli Chapman, A.A. Leslie Gunatilaka
Incorporation of the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), to a culture broth of the endophytic fungus Phoma sp. nov. LG0217 isolated from Parkinsonia microphylla changed its metabolite profile and resulted in the production of (10'S)-verruculide B (1), vermistatin (2) and dihydrovermistatin (3). When cultured in the absence of the epigenetic modifier, it produced a new metabolite, (S,Z)-5-(3',4'-dihydroxybutyldiene)-3-propylfuran-2(5H)-one (4) together with nafuredin (5). The structure of 4 was elucidated by spectroscopic analyses and its absolute configuration was determined by application of the modified Mosher's ester method. The absolute structure of (10'S)-verruculide B was determined as 5-[(10'S,2'E,6'E)-10',11'-dihydroxy-3',7',11'-trimethyldodeca-2',6'-dien-1'-yl]-(3R)-6,8-dihydroxy-3-methylisochroman-1-one (1) with the help of CD and NOE data. Compound 1 inhibited the activity of protein tyrosine phosphatases (PTPs) 1B (PTP1B), Src homology 2-containing PTP 1 (SHP1) and T-cell PTP (TCPTP) with IC50 values of 13.7±3.4, 8.8±0.6, and 16.6±3.8 μM, respectively. Significance of these activities and observed modest selectivity of 1 for SHP1 over PTP1B and TCPTP is discussed.

Graphical abstract

http://ift.tt/2l919EB

Non-receptor type, proline-rich protein tyrosine kinase 2 (Pyk2) is a possible therapeutic target for Kawasaki disease

Publication date: Available online 3 February 2017
Source:Clinical Immunology
Author(s): Chinatsu Suzuki, Akihiro Nakamura, Noriko Miura, Kunityoshi Fukai, Naohito Ohno, Tomoyo Yahata, Akiko Okamoto-Hamaoka, Maiko Fujii, Ayako Yoshioka, Yuki Kuchitsu, Kazuyuki Ikeda, Kenji Hamaoka
Kawasaki disease (KD) is a paediatric vasculitis whose pathogenesis remains unclear. Based on experimental studies using a mouse model for KD, we report here that proline-rich protein tyrosine kinase 2 (Pyk2) plays a critical role in the onset of KD-like murine vasculitis.The mouse model for KD was prepared by administrating a Candida albicans water-soluble fraction (CAWS). Unlike CAWS-treated WT mice, CAWS-treated Pyk2-Knockout (Pyk2-KO) mice did not develop apparent vasculitis. A sustained increase in MIG/CXCL9 and IP-10/CXCL10, both of which have potent "angiostatic" activity, was observed in CAWS-treated Pyk2-KO mice. CAWS-induced activation of STAT3, which negatively regulates the expression of these chemokines, was also attenuated in macrophages derived from Pyk2-KO mice.The present study suggests that defects in Pyk2 suppress KD-like experimental vasculitis, presumably through CXCL9- and CXCL10-dependent interference with neo-angiogenesis. Since Pyk2-KO mice show no life-threatening phenotype, Pyk2 may be a promising therapeutic target for KD.(147/150 words)



http://ift.tt/2l8Y7Ad

Long-term safety and efficacy of Omnitrope ® in adults with growth hormone deficiency: Italian interim analysis of the PATRO Adults study

Abstract

Purpose

To report the long-term effectiveness and safety of the recombinant human growth hormone Omnitrope^®, a somatropin biosimilar to Genotropin^®, in Italian patients with growth hormone deficiency (GHD) enrolled in the PATRO Adults study.

Methods

The PATRO Adults study is an ongoing observational, longitudinal, non-interventional global post-marketing surveillance study, conducted in several European countries. The primary endpoint is long-term safety; secondary endpoints include the effectiveness of Omnitrope^®, which was assessed using serum insulin-like growth factor-1 levels, body composition, bone mineral density and lipid levels. Here we report the data from the Italian patients enrolled in the study.

Results

Sixty-seven patients (mean age 50.4 years, 61.2% male) have been enrolled and have received a mean 45.4 ± 24.3 months of Omnitrope^®. A total of 55.2% of patients were reported to have experienced adverse events (AEs), including arthralgia, myalgia, abdominal distension and hypoaesthesia, and 4.5% had adverse drug reactions. Fourteen serious AEs have been recorded; none of these are considered related to the study drug. The effectiveness of Omnitrope^® was similar to other available somatropin preparations.

Conclusions

This study confirms the effectiveness and safety of Omnitrope^® in adult patients with GHD in Italy. However, due to the limited size of the study population, these results need to be further confirmed by the global PATRO Adults study.

http://ift.tt/2k6D7tu

Hypothalamic Tumors Impact Grey and White Matter Volumes in Fronto-Limbic Brain Areas

Publication date: Available online 3 February 2017
Source:Cortex
Author(s): Jale Özyurt, Hermann L. Müller, Monika Warmuth-Metz, Christiane M. Thiel
Patients with hypothalamic involvement of a sellar/parasellar tumor often suffer from cognitive and social-emotional deficits that a lesion in the hypothalamus cannot fully explain. It is conceivable that these deficits are partly due to distal changes in hypothalamic networks, evolving secondary to a focal lesion. Focusing on childhood-onset craniopharyngioma patients, we aimed at investigating the impact of hypothalamic lesions on grey and white matter areas densely connected to the hypothalamus, and to relate structural changes to neuropsychological deficits frequently observed in patients.We performed a voxel-based morphometric analysis based on data of 11 childhood-onset craniopharyngioma patients with hypothalamic tumor involvement, and 18 healthy controls (median age: 17.2 and 17.4 yrs.). Whole-brain analyses were used to test for volumetric differences between the groups (T-tests) and subsequent regression analyses were used to correlate neuropsychological performance with grey and white matter volumes within the patient group.Patients compared to controls had significantly reduced grey matter volumes in areas of the anterior and posterior limbic subsystems which are densely connected with the hypothalamus. In addition, a reduction in white matter volumes was observed in tracts connecting the hypothalamus to other limbic areas. Worse long-term memory retrieval was correlated with smaller grey matter volumes in the posterior cingulate cortex.Our data provide the first evidence that hypothalamic tumor involvement impacts grey and white matter volumes in limbic areas, outside the area of tumor growth. Notably, the functional range of the two limbic subsystems affected, strikingly parallels the two major domains of psychological complaints in patients i.e. deficits in episodic memory and in socio-emotional functioning. We suggest that focal hypothalamic lesions may trigger distal changes in connected brain areas, which then contribute to the impairments in cognitive, social and emotional performance often observable in patients, and not explicable by a hypothalamic lesion alone.



http://ift.tt/2l8gyph

Cross-Cultural Differences in the Neural Correlates of Specific and General Recognition

Publication date: Available online 3 February 2017
Source:Cortex
Author(s): Laura E. Paige, John C. Ksander, Hunter A. Johndro, Angela H. Gutchess
Research suggests that culture influences how people perceive the world, which extends to memory specificity, or how much perceptual detail is remembered. The present study investigated cross-cultural differences (Americans vs. East Asians) at the time of encoding in the neural correlates of specific vs. general memory formation. Participants encoded photos of everyday items in the scanner and 48 hours later completed a surprise recognition test. The recognition test consisted of same (i.e., previously seen in scanner), similar (i.e., same name, different features), or new photos (i.e., items not previously seen in scanner). For Americans compared to East Asians, we predicted greater activation in the hippocampus and right fusiform for specific memory at recognition, as these regions were implicated previously in encoding perceptual details. Results revealed that East Asians activated the left fusiform and left hippocampus more than Americans for specific vs. general memory. Follow-up analyses ruled out alternative explanations of retrieval difficulty and familiarity for this pattern of cross-cultural differences at encoding. Results overall suggest that culture should be considered as another individual difference that affects memory specificity and modulates neural regions underlying these processes.



http://ift.tt/2kDYNR6

Prognostic impact of EGFR and cytokeratin 5/6 immunohistochemical expression in triple-negative breast cancer

Publication date: Available online 4 February 2017
Source:Annals of Diagnostic Pathology
Author(s): Aziza E. Abdelrahman, Hayam E. Rashed, Mohamed Abdelgawad, Mohamed I. Abdelhamid




http://ift.tt/2kzMAgD

Emotion Perception from Face, Voice, and Touch: Comparisons and Convergence

Publication date: Available online 4 February 2017
Source:Trends in Cognitive Sciences
Author(s): Annett Schirmer, Ralph Adolphs
Historically, research on emotion perception has focused on facial expressions, and findings from this modality have come to dominate our thinking about other modalities. Here we examine emotion perception through a wider lens by comparing facial with vocal and tactile processing. We review stimulus characteristics and ensuing behavioral and brain responses and show that audition and touch do not simply duplicate visual mechanisms. Each modality provides a distinct input channel and engages partly nonoverlapping neuroanatomical systems with different processing specializations (e.g., specific emotions versus affect). Moreover, processing of signals across the different modalities converges, first into multi- and later into amodal representations that enable holistic emotion judgments.



http://ift.tt/2jLgCOO

Social Learning in the Medial Prefrontal Cortex

Publication date: Available online 4 February 2017
Source:Trends in Cognitive Sciences
Author(s): Matthew A.J. Apps, Jérôme Sallet
The ACC, and neighbouring areas, are among the most controversial and investigated brain areas in cognitive neuroscience. Despite the wealth of studies, there has been a significant absence of studies recording from the gyrus of the ACC (ACCg). In their recent study Hill and colleagues provide a rare examination of the properties of the ACCg. We highlight the emerging role of this region in signalling the key computations that drive social learning processes.



http://ift.tt/2l8dIkj

Long-lasting effects of fluoxetine and/or exercise augmentation on bio-behavioural markers of depression in pre-pubertal stress sensitive rats

Publication date: 14 April 2017
Source:Behavioural Brain Research, Volume 323
Author(s): Jacobus C. Schoeman, Stephanus F. Steyn, Brian H. Harvey, Christiaan B. Brink
Juvenile depression is of great concern with only limited treatment currently approved. Delayed onset of action, low remission and high relapse rates, and potential long-lasting consequences further complicates treatment and highlights the need for new treatment options. Studies reporting on long-lasting effects of early-life treatment have reported conflicting results, with the pre-adolescent period mostly overlooked. The anti-depressive effect of exercise, as a possible treatment option or augmentation strategy, is dependent on age and exercise intensity. We investigated the immediate (i.e. postnatal day 35 (PND35)) and lasting (PND60 to PND61) effects of pre-pubertal (PND21 to PND34) fluoxetine and/or exercise on bio-behavioural markers of depression and oxidative stress in stress sensitive Flinders Sensitive Line rats. Low, but not moderate, intensity exercise or 5, but not 10, mg/kg/day fluoxetine displayed anti-depressant-like properties at PND35. Pre-pubertal treatment with 5mg/kg/day fluoxetine or low intensity exercise exerted lasting anti-depressive-like effects into adulthood, whereas the combination of these two treatments did not. Furthermore, the combination of fluoxetine plus exercise reduced hippocampal BDNF levels as compared to exercise alone, which may explain the latter findings. In all treatment groups hippocampal SOD activity was significantly increased at PND61, suggesting an increased anti-oxidant capacity in adulthood. In conclusion, the data confirm the anti-depressant-like properties of both early-life fluoxetine and exercise in a genetic animal model of depression. However, optimal lasting effects of early-life interventions may require adjustment of antidepressant dose and/or exercise intensity to developmental age, and that a combination of antidepressant and exercise may not necessarily be augmentative.



http://ift.tt/2jL94f5

The value of adaptive preoperative radiotherapy in management of soft tissue sarcoma

Publication date: Available online 4 February 2017
Source:Radiotherapy and Oncology
Author(s): Colleen Dickie, Amy Parent, Anthony M. Griffin, Jay Wunder, Peter Ferguson, Peter W. Chung, Tim Craig, Michael Sharpe, Nathan Becker, David Shultz, Charles N. Catton, Brian O'Sullivan
PurposeTo determine the value of preoperative adaptive radiotherapy (ART) for soft tissue sarcoma patients (STS) by modeling the dosimetric consequences of tumour volume changes (TVC) using different external beam radiotherapy techniques.Methods and materialsA subset of 22 STS patients from a recent trial (NCT00188175) underwent a repeat CT scan (CT2) prompted by TVC>1cm during IMRT; 14 tumours grew, 8 shrank. Conformal and conventional plans were modelled in addition to IMRT replicating original criteria from the initial planning dataset (CT1):95% PTV encompassed by 97% prescribed dose. CT1 RT parameters for all plans were applied to CT2 for dosimetric assessment of TVC. Co-registration of CT1 and CT2 permitted comparison of original and new contours.ResultsMean TVC was 45% for growing and 33% for the shrinking cohort with TVC prompting CT2 at a mean of 13 fractions. For growers, the lack of target coverage on CT2 was statistically significant but was adequate for shrinkers.ConclusionGTV expansion of >1cm during RT may result in target underdosage independent of RT technique. ART applied offline for TV increases >1cm is a practical adaptive strategy to ensure tumour coverage during RT. TV shrinkage may allow for normal tissue sparing, which should be investigated prospectively.



http://ift.tt/2jOaZKP

Nomogram based overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease

Publication date: Available online 4 February 2017
Source:Radiotherapy and Oncology
Author(s): S. Tanadini-Lang, J. Rieber, A.R. Filippi, M.M. Fode, J. Streblow, S. Adebahr, N. Andratschke, O. Blanck, J. Boda-Heggemann, M. Duma, M.J. Eble, I. Ernst, M. Flentje, S. Gerum, P. Hass, C. Henkenberens, G. Hildebrandt, D. Imhoff, H. Kahl, N.D. Klass, R. Krempien, F. Lohaus, C. Petersen, E. Schrade, T.G. Wendt, A. Wittig, M. Høyer, U. Ricardi, F. Sterzing, M. Guckenberger
BackgroundRadical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases.Patients and methodsA multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan–Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases.ResultsThe median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all p<0.05). The calculated concordance-index for the nomogram was 0.73 (concordance indexes of all prognostic factors between 0.54 and 0.6). Based on the nomogram the training cohort was divided into 4 groups and 2-year OS ranged between 24.2% and 76.1% (predicted OS between 30.2% and 78.4%). The nomogram discriminated between risk groups in the two validation cohorts (concordance index 0.68 and 0.67).ConclusionsA nomogram for prediction of OS after SBRT for pulmonary metastases was generated and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.Key messageA nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.



http://ift.tt/2jKP0JD

DERMOSCOPIC FEATURES PREDICTING THE PRESENCE OF MITOSES IN THIN MELANOMA

Publication date: Available online 3 February 2017
Source:Journal of Dermatological Science
Author(s): S. Ribero, G. Argenziano, A. Lallas, E. Moscarella, E. Benati, M. Raucci, S. Piana, C. Longo
BACKGROUNDThe latest AJCC classification has included the number of mitoses as a factor for upstaging thin melanomas. Meanwhile, while dermoscopy has often been used to predict melanoma thickness, its value in predicting number of mitoses remains unknown.OBJECTIVEOur aim is to evaluate the correlation between dermoscopic features and the presence of mitoses in a consecutive cohort of thin melanomas.METHODS. A case control study has been performed to identify specific dermoscopic parameters that could differentiate thin melanomas with 1 or more mitoses per mm2 from those without mitoses.RESULTSOf 177 melanomas equal to or thinner than 1mm, 131 (74%) lesions had no mitoses and 46 (36%) lesions had at least 1 mitosis x mm2. Dermoscopic features associated with the presence of 1 or more mitoses were the following: peripheral streaks (OR 4.11; 95% CI 1.94-8.71) and black colour (OR 4.70; 95% CI; 2.28-9.68). In contrast, atypical pigment network (OR (0.30; 95% CI 0.15-0.61) and brown colour (OR 0.36; 95%CI 0.18-0.75) were associated to melanomas without mitoses. The same variables were also associated to the increasing number of mitoses at linear regression.CONCLUSIONBlack colour and peripheral streaks can predict the presence of mitoses in thin melanoma, while atypical pigment network and brown colour are associated to thin melanoma without mitoses.



http://ift.tt/2l8MI30

Autophagy Receptors and Neurodegenerative Diseases

Publication date: Available online 3 February 2017
Source:Trends in Cell Biology
Author(s): Zhiqiang Deng, Kerry Purtell, Veronik Lachance, Mitchell S. Wold, Shi Chen, Zhenyu Yue
Previously thought of as a nonselective digestion process, autophagy is now known to specifically degrade aggregated proteins and damaged cellular organelles through the action of autophagy receptors, which provides cellular quality control and maintains homeostasis. Autophagy receptors recognize and recruit specific cargoes to the autophagosome–lysosome pathway for degradation in ubiquitin-dependent and -independent manners, and their functions (in selective autophagy) are regulated by protein modifications, for example, phosphorylation and ubiquitination. Growing evidence has linked the genetic variants of autophagy receptors to neurodegenerative diseases and multiple experimental systems have validated their roles in modulating the disease process. Here, we review the recent advances in understanding the physiology and pathophysiology of autophagy receptors in selective autophagy, and discuss their potentials as therapeutic targets for neurodegenerative diseases.



http://ift.tt/2l8CtMm

A visible and colorimetric aptasensor based on DNA-capped single-walled carbon nanotubes for detection of exosomes

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Yaokun Xia, Mengmeng Liu, Liangliang Wang, An Yan, Wenhui He, Mei Chen, Jianming Lan, Jiaoxing Xu, Lunhui Guan, Jinghua Chen
Recently, many studies have shown the potential use of circulating exosomes as novel biomarkers for monitoring and predicting a number of complex diseases, including cancer. However, reliable and cost-effective detection of exosomes in routine clinical settings, still remain a difficult task, mainly due to the lack of adequately easy and fast assay platforms. Therefore, we demonstrate here the development of a visible and simple method for the detection of exosomes by integrating single-walled carbon nanotubes that being excellent water solubility (s-SWCNTs) and aptamer. Aptamers, specific to exosomes transmembrane protein CD63, are absorbed onto the surface of s-SWCNTs and improve the minic peroxidase activity of s-SWCNTs, which can efficiently catalyze H2O2-mediated oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) and lead to a change from colorless to blue in solution. However, after adding exosomes, the aptamers are bound with CD63, leaving from the surface of s-SWCNTs through conformational changes, which results the color of solution from deep to moderate, and this can be observed by the naked eye and monitored by UV–vis spectrometry. Under optimal conditions, the linear range of exosomes is estimated to be 1.84×10⁶ to 2.21×10⁷ particles/μL with a detection of limit (LOD) of 5.2×10⁵ particles/μL. Consequently, a visible and simple approach detecting exosomes is successfully constructed. Moreover, this proposed colorimetric aptasensor can be universally applicable for the detection of other targets by simple change the aptamer.



http://ift.tt/2l8pytC

Fluorescence enhancement of CdTe quantum dots by HBcAb-HRP for sensitive detection of H2O2 in human serum

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Tingting Gong, Junfeng Liu, Yiwei Wu, Yao Xiao, Xuehan Wang, Siqi Yuan
A simple, high selective, ultra-sensitive and stable biosensor based on hepatitis B core antibody labeled with horseradish peroxidase (HBcAb-HRP) induced fluorescent enhancement of CdTe QDs for recognition of H2O2 have been constructed. In this assay, sulfurs in HBcAb-HRP, which possess a strong affinity towards Cd²⁺, can improve greatly the recombination fluorescence of CdTe QDs by creating more radiative centers at CdTe/Cd-SR complex. Then, H2O2 oxidizes Cd-S bonds in CdTe QDs to organic disulfide product (RS-SR), causing thioglycolic acid (TGA) and HBcAb-HRP detach from surface of CdTe QDs and thus leading to fluorescence quenching. Just with the addition of HBcAb-HRP, sensitivity of the new biosensor has been improved by near one order of magnitude as compared with CdTe QDs probe. Detection limit of HBcAb-HRP-CdTe QDs biosensor for determination of H2O2 was 6.9×10⁻⁸mol L⁻¹ (3σ/slope), and the excellent linear range was 1.0×10⁻⁷~1.5×10⁻⁴molL⁻¹. By using sodium diethyldithiocarbamate (DDTC) and NH4OH as masking agents of Ag⁺, Hg²⁺ and Cu²⁺, H2O2 can be selectively detected in coexistence with Ag⁺, Hg²⁺ and Cu²⁺, and the biosensor has been used to detect H2O2 in human serum with satisfactory results. The superior properties of this biosensor showed great potential usage in more chemical and biological researches.



http://ift.tt/2kDK1K5

Label-free immunosensor based on hyperbranched polyester for specific detection of α-fetoprotein

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Yanlian Niu, Tian Yang, Shangshang Ma, Fang Peng, Meihui Yi, Mimi Wan, Chun Mao, Jian Shen
A novel label-free immunosensor based on hyperbranched polyester nanoparticles with nitrite groups (HBPE-NO2), which were synthesized through a simple one-step chemical reaction, was first developed for specific detection of α-fetoprotein (AFP), the tumor marker for liver cancer. The obtained HBPE-NO2 nanoparticles (NPs) were characterized by the proton nuclear magnetic resonance spectroscopy (¹H NMR), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). And the fabricated process of immunosensor was investigated by attenuated total reflection Fourier-transform infrared spectra (ATR-FTIR), static water contact angles, scanning electron microscope (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The electrochemical performances of the AFP immunosensor were studied. Results indicated the prepared HBPE-NO2-modified immunosensor showed excellent electrochemical properties and satisfactory accuracy for the detection of AFP of the real clinical samples that attributed to the properties of the HBPE-NO2 NPs, which had nanosized structure to increase the specific surface area and unique chemical reactivity for loading capacity of protein molecules. Construction of biosensors using the structure and properties of hyperbranched molecules will offer ideal electrode substrates, which provided more possibilities for the design of biosensor.



http://ift.tt/2jJcHC3

Reversal of P-glycoprotein-mediated multidrug resistance is induced by saikosaponin D in breast cancer MCF-7/adriamycin cells

Publication date: Available online 3 February 2017
Source:Pathology - Research and Practice
Author(s): Chun Li, Xingang Guan, Haogang Xue, Peng Wang, Manli Wang, Xiaodong Gai
Multidrug resistance (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene is major obstacles for successful cancer chemotherapy. P-gp could extrude anti-cancer drugs out of cancer cells and decrease effective intracellular drug concentrations. MDR reversal agents for P-gp can restore the sensitivity of MDR cells to such drugs. Saikosaponin D (SSd), one of the major triterpenoid saponins derived from Bupleurum chinense DC (BCDC), has been shown to possess anti-inflammatory, anti-infectious and anti-tumor properties. The aim of the present study was to investigate the reversal effect of SSd on MDR in MCF-7/adriamycin (ADR) human breast cancer cells and investigate the underlying mechanisms of SSd. The results demonstrated that SSd inhibited the proliferation of MCF-7/ADR and MCF-7 cells in a dose-dependent manner. Moreover, SSd increased the cytotoxicity of ADR on MCF-7/ADR cells and the resistance fold of SSd treatment was demonstrated to be significantly higher when compared with that of the group without SSd treatment. Additionally, the effects of the drug combination showed that SSd and ADR combination were synergistic. Accumulation and efflux studies with the P-gp substrate, rhodamine 123 (Rh123), demonstrated that SSd restored Rh123 accumulation and inhibited P-gp-mediated drug efflux. Importantly, we found that SSd could enhance the sensitivity of MCF-7/ADR cells towards ADR by down-regulating MDR1 and P-gp expression. In conclusion, the results of the present study indicated that SSd may represent a potent reversal agent for P-gp-mediated MDR in breast cancer therapy.



http://ift.tt/2l7H3eK

“With a little help from my friends” - The role of microbiota in thyroid hormone metabolism and enterohepatic recycling

Publication date: Available online 4 February 2017
Source:Molecular and Cellular Endocrinology
Author(s): Camilla Virili, Marco Centanni
The gut microbiota is composed of over 1200 species of anaerobes and aerobes bacteria along with bacteriophages, viruses and fungal species. Increasing evidence indicates that the intestinal microbiota, beside digestive equilibrium, is also crucial for immunologic, hormonal and metabolic homeostasis. The intestinal microbiota interacts with distant organs by signals which may be part of the bacteria themselves or their metabolites. Dysbiosis has been observed in inflammatory or autoimmune disorders such as multiple sclerosis or type 1 diabetes as well as in obesity and type 2 diabetes. Functional thyroid disorders were associated with bacterial overgrowth and a different microbial composition. Although thyroid metabolism was apparently disregarded, the interference of microbiota on peripheral iodothyronine homeostasis is an intriguing issue. In this review we focused on the interactions of intestinal microbiota with thyroid-related micronutrients and with the metabolic steps of endogenous and exogenous iodothyronines.

Graphical abstract

http://ift.tt/2jKHSwP

β-arrestin signalling and bias in hormone-responsive GPCRs

Publication date: Available online 4 February 2017
Source:Molecular and Cellular Endocrinology
Author(s): Eric Reiter, Mohammed Akli Ayoub, Lucie P. Pellissier, Flavie Landomiel, Astrid Musnier, Aurélie Tréfier, Jorge Gandia, Francesco De Pascali, Shifa Tahir, Romain Yvinec, Gilles Bruneau, Anne Poupon, Pascale Crépieux
G protein-coupled receptors (GPCRs) play crucial roles in the ability of target organs to respond to hormonal cues. GPCRs' activation mechanisms have long been considered as a two-state process connecting the agonist-bound receptor to heterotrimeric G proteins. This view is now challenged as mounting evidence point to GPCRs being connected to large arrays of transduction mechanisms involving heterotrimeric G proteins as well as other players. Amongst the G protein-independent transduction mechanisms, those elicited by β-arrestins upon their recruitment to the active receptors are by far the best characterized and apply to most GPCRs. These concepts, in conjunction with remarkable advances made in the field of GPCR structural biology and biophysics, have supported the notion of ligand-selective signalling also known as pharmacological bias. Interestingly, recent reports have opened intriguing prospects to the way β-arrestins control GPCR-mediated signalling in space and time within the cells. In the present paper, we review the existing evidence linking endocrine-related GPCRs to β-arrestin recruitement, signalling, pathophysiological implications and selective activation by biased ligands and/or receptor modifications. Emerging concepts surrounding β-arrestin-mediated transduction are discussed in the light of the peculiarities of endocrine systems.



http://ift.tt/2jKBS7l

The therapeutic contribution of nanomedicine to treat neurodegenerative diseases via neural stem cell differentiation

Publication date: April 2017
Source:Biomaterials, Volume 123
Author(s): Dario Carradori, Joel Eyer, Patrick Saulnier, Véronique Préat, Anne des Rieux
The discovery of adult neurogenesis drastically changed the therapeutic approaches of central nervous system regenerative medicine. The stimulation of this physiologic process can increase memory and motor performances in patients affected by neurodegenerative diseases. Neural stem cells contribute to the neurogenesis process through their differentiation into specialized neuronal cells. In this review, we describe the most important methods developed to restore neurological functions via neural stem cell differentiation. In particular, we focused on the role of nanomedicine. The application of nanostructured scaffolds, nanoparticulate drug delivery systems, and nanotechnology-based real-time imaging has significantly improved the safety and the efficacy of neural stem cell-based treatments. This review provides a comprehensive background on the contribution of nanomedicine to the modulation of neurogenesis via neural stem cell differentiation.

Graphical abstract

http://ift.tt/2ka68XC

Biodegradable scaffolds promote tissue remodeling and functional improvement in non-human primates with acute spinal cord injury

Publication date: April 2017
Source:Biomaterials, Volume 123
Author(s): Jonathan R. Slotkin, Christopher D. Pritchard, Brian Luque, Janice Ye, Richard T. Layer, Mathew S. Lawrence, Timothy M. O'Shea, Roland R. Roy, Hui Zhong, Isabel Vollenweider, V. Reggie Edgerton, Grégoire Courtine, Eric J. Woodard, Robert Langer
Tissue loss significantly reduces the potential for functional recovery after spinal cord injury. We previously showed that implantation of porous scaffolds composed of a biodegradable and biocompatible block copolymer of Poly-lactic-co-glycolic acid and Poly-l-lysine improves functional recovery and reduces spinal cord tissue injury after spinal cord hemisection injury in rats. Here, we evaluated the safety and efficacy of porous scaffolds in non-human Old-World primates (Chlorocebus sabaeus) after a partial and complete lateral hemisection of the thoracic spinal cord. Detailed analyses of kinematics and muscle activity revealed that by twelve weeks after injury fully hemisected monkeys implanted with scaffolds exhibited significantly improved recovery of locomotion compared to non-implanted control animals. Twelve weeks after injury, histological analysis demonstrated that the spinal cords of monkeys with a hemisection injury implanted with scaffolds underwent appositional healing characterized by a significant increase in remodeled tissue in the region of the hemisection compared to non-implanted controls. The number of glial fibrillary acidic protein immunopositive astrocytes was diminished within the inner regions of the remodeled tissue layer in treated animals. Activated macrophage and microglia were present diffusely throughout the remodeled tissue and concentrated at the interface between the preserved spinal cord tissue and the remodeled tissue layer. Numerous unphosphorylated neurofilament H and neuronal growth associated protein positive fibers and myelin basic protein positive cells may indicate neural sprouting inside the remodeled tissue layer of treated monkeys. These results support the safety and efficacy of polymer scaffolds in a primate model of acute spinal cord injury. A device substantially similar to the device described here is the subject of an ongoing human clinical trial.



http://ift.tt/2kcsWpT

Silk-based anisotropical 3D biotextiles for bone regeneration

Publication date: April 2017
Source:Biomaterials, Volume 123
Author(s): Viviana P. Ribeiro, Joana Silva-Correia, Ana I. Nascimento, Alain da Silva Morais, Alexandra P. Marques, Ana S. Ribeiro, Carla J. Silva, Graça Bonifácio, Rui A. Sousa, Joaquim M. Oliveira, Ana L. Oliveira, Rui L. Reis
Bone loss in the craniofacial complex can been treated using several conventional therapeutic strategies that face many obstacles and limitations. In this work, novel three-dimensional (3D) biotextile architectures were developed as a possible strategy for flat bone regeneration applications. As a fully automated processing route, this strategy as potential to be easily industrialized. Silk fibroin (SF) yarns were processed into weft-knitted fabrics spaced by a monofilament of polyethylene terephthalate (PET). A comparative study with a similar 3D structure made entirely of PET was established. Highly porous scaffolds with homogeneous pore distribution were observed using micro-computed tomography analysis. The wet state dynamic mechanical analysis revealed a storage modulus In the frequency range tested, the storage modulus values obtained for SF-PET scaffolds were higher than for the PET scaffolds. Human adipose-derived stem cells (hASCs) cultured on the SF-PET spacer structures showed the typical pattern for ALP activity under osteogenic culture conditions. Osteogenic differentiation of hASCs on SF-PET and PET constructs was also observed by extracellular matrix mineralization and expression of osteogenic-related markers (osteocalcin, osteopontin and collagen type I) after 28 days of osteogenic culture, in comparison to the control basal medium. The quantification of convergent macroscopic blood vessels toward the scaffolds by a chick chorioallantoic membrane assay, showed higher angiogenic response induced by the SF-PET textile scaffolds than PET structures and gelatin sponge controls. Subcutaneous implantation in CD-1 mice revealed tissue ingrowth's accompanied by blood vessels infiltration in both spacer constructs. The structural adaptability of textile structures combined to the structural similarities of the 3D knitted spacer fabrics to craniofacial bone tissue and achieved biological performance, make these scaffolds a possible solution for tissue engineering approaches in this area.



http://ift.tt/2ksd2q2

Bioengineered three-dimensional diseased intervertebral disc model revealed inflammatory crosstalk

Publication date: April 2017
Source:Biomaterials, Volume 123
Author(s): Akshay Srivastava, Isma Liza Mohd Isa, Peadar Rooney, Abhay Pandit
Without an appropriate disease model, the understanding of the pathophysiology of intervertebral disc degeneration and inflammation is limited. The lack of understanding limits the potential discovery of therapeutic targets as viable treatment options. Here, we report a versatile method to develop a three-dimensional intervertebral disc (IVD) model to study the response of nucleus pulposus (NP) and annulus fibrosus (AF) cells to inflammatory (IL-1β-induced) stimulation. The cell shape regulated IVD model was engineered by modulating the crosslinking of a self-assembled collagen hydrogel. The developed model has provided us with an understanding of the molecular changes that occur at genetic level which modulate the production of extracellular matrix components and key inflammatory pathways in the inflamed IVD. We have identified the role of the suppressor of cytokine proteins (SOCS) family in combating detrimental effects of pro-inflammatory cytokines in degenerated human NP tissue as predicted by the developed diseased model. The model could also provide an understanding of the expression of glycans implicated in the diseased IVD.



http://ift.tt/2l8ecG7

Perivascular extracellular matrix hydrogels mimic native matrix microarchitecture and promote angiogenesis via basic fibroblast growth factor

Publication date: April 2017
Source:Biomaterials, Volume 123
Author(s): George R. Fercana, Saigopalakrishna Yerneni, Marie Billaud, Jennifer C. Hill, Paul VanRyzin, Tara D. Richards, Brian M. Sicari, Scott A. Johnson, Stephen F. Badylak, Phil G. Campbell, Thomas G. Gleason, Julie A. Phillippi
Extracellular matrix (ECM)-derived bioscaffolds have been shown to elicit tissue repair through retention of bioactive signals. Given that the adventitia of large blood vessels is a richly vascularized microenvironment, we hypothesized that perivascular ECM contains bioactive signals that influence cells of blood vessel lineages. ECM bioscaffolds were derived from decellularized human and porcine aortic adventitia (hAdv and pAdv, respectively) and then shown have minimal DNA content and retain elastin and collagen proteins. Hydrogel formulations of hAdv and pAdv ECM bioscaffolds exhibited gelation kinetics similar to ECM hydrogels derived from porcine small intestinal submucosa (pSIS). hAdv and pAdv ECM hydrogels displayed thinner, less undulated, and fibrous microarchitecture reminiscent of native adventitia, with slight differences in ultrastructure visible in comparison to pSIS ECM hydrogels. Pepsin-digested pAdv and pSIS ECM bioscaffolds increased proliferation of human adventitia-derived endothelial cells and this effect was mediated in part by basic fibroblast growth factor (FGF2). Human endothelial cells cultured on Matrigel substrates formed more numerous and longer tube-like structures when supplemented with pAdv ECM bioscaffolds, and FGF2 mediated this matrix signaling. ECM bioscaffolds derived from pAdv promoted FGF2-dependent in vivo angiogenesis in the chick chorioallantoic membrane model. Using an angiogenesis-focused protein array, we detected 55 angiogenesis-related proteins, including FGF2 in hAdv, pAdv and pSIS ECMs. Interestingly, 19 of these factors were less abundant in ECMs bioscaffolds derived from aneurysmal specimens of human aorta when compared with non-aneurysmal (normal) specimens. This study reveals that Adv ECM hydrogels recapitulate matrix fiber microarchitecture of native adventitia, and retain angiogenesis-related actors and bioactive properties such as FGF2 signaling capable of influencing processes important for angiogenesis. This work supports the use of Adv ECM bioscaffolds for both discovery biology and potential translation towards microvascular regeneration in clinical applications.



http://ift.tt/2kcpwUh

Engineering of a hybrid nanoparticle-based nicotine nanovaccine as a next-generation immunotherapeutic strategy against nicotine addiction: A focus on hapten density

Publication date: April 2017
Source:Biomaterials, Volume 123
Author(s): Zongmin Zhao, Kristen Powers, Yun Hu, Michael Raleigh, Paul Pentel, Chenming Zhang
Although vaccination is a promising way to combat nicotine addiction, most traditional hapten-protein conjugate nicotine vaccines only show limited efficacy due to their poor recognition and uptake by immune cells. This study aimed to develop a hybrid nanoparticle-based nicotine vaccine with improved efficacy. The focus was to study the impact of hapten density on the immunological efficacy of the proposed hybrid nanovaccine. It was shown that the nanovaccine nanoparticles were taken up by the dendritic cells more efficiently than the conjugate vaccine, regardless of the hapten density on the nanoparticles. At a similar hapten density, the nanovaccine induced a significantly stronger immune response against nicotine than the conjugate vaccine in mice. Moreover, the high- and medium-density nanovaccines resulted in significantly higher anti-nicotine antibody titers than their low-density counterpart. Specifically, the high-density nanovaccine exhibited better immunogenic efficacy, resulting in higher anti-nicotine antibody titers and lower anti-carrier protein antibody titers than the medium- and low-density versions. The high-density nanovaccine also had the best ability to retain nicotine in serum and to block nicotine from entering the brain. These results suggest that the hybrid nanoparticle-based nicotine vaccine can elicit strong immunogenicity by modulating the hapten density, thereby providing a promising next-generation immunotherapeutic strategy against nicotine addiction.

Graphical abstract

http://ift.tt/2ks7QT1

Hyper-cell-permeable micelles as a drug delivery carrier for effective cancer therapy

Publication date: April 2017
Source:Biomaterials, Volume 123
Author(s): Phei Er Saw, Mikyung Yu, Minsuk Choi, Eunbeol Lee, Sangyong Jon, Omid C. Farokhzad
Although PEGylated liposomes (PEG-LS) have been intensively studied as drug-delivery vehicles, the rigidity and the hydrophilic PEG corona of liposomal membranes often limits cellular uptake, resulting in insufficient drug delivery to target cells. Thus, it is necessary to develop a new type of lipid-based self-assembled nanoparticles capable of enhanced cellular uptake, tissue penetration, and drug release than conventional PEGylated liposomes. Herein, we describe a simple modification of bicellar formulation in which the addition of a PEGylated phospholipid produced a dramatic physicochemical change in morphology, i.e., the disc-shaped bicelle became a uniformly distributed ultra-small (∼12 nm) spherical micelle. The transformed lipid-based nanoparticles, which we termed hyper-cell-permeable micelles (HCPMi), demonstrated not only prolonged stability in serum but also superior cellular and tumoral uptake compared to a conventional PEGylated liposomal system (PEG-LS). In addition, HCPMi showed rapid cellular uptake and subsequent cargo release into the cytoplasm of cancer cells. Cells treated with HCPMi loaded with docetaxel (DTX) had an IC50 value of 0.16 μM, compared with 0.78 μM with PEG-LS loaded with DTX, a nearly five-fold decrease in cell viability, indicating excellent efficiency in HCPMi uptake and release. In vivo tumor imaging analysis indicated that HCPMi penetrated deep into the tumor core and achieved greater uptake than PEG-LS. Results of HCPMi (DTX) treatment of allograft and xenograft mice in vivo showed high tumoral uptake and appreciable tumor retardation, with ∼70% tumor weight reduction in the SCC-7 allograft model. Taken together, these findings indicate that HCPMi could be developed further as a highly competent lipid-based drug-delivery system.

Graphical abstract

http://ift.tt/2ksiZD9

NMDA receptor adjusted co-administration of ecstasy and cannabinoid receptor-1 agonist in the amygdala via stimulation of BDNF/Trk-B/CREB pathway in adult male rats

Publication date: Available online 3 February 2017
Source:Brain Research Bulletin
Author(s): Ghorbangol Ashabi, Mitra-Sadat Sadat-Shirazi, Solmaz Khalifeh, Laleh Elhampour, Mohammad-Reza Zarrindast
Consumption of cannabinoid receptor-1 (CB-1) agonist such as cannabis is widely taken in 3,4- methylenedioxymethamphetamine (MDMA) or ecstasy users; it has been hypothesized that co-consumption of CB-1 agonist might protect neurons against MDMA toxicity. N-methyl-D-aspartate (NMDA) receptors regulate neuronal plasticity and firing rate in the brain through Tyrosine-kinase B (Trk-B) activation. The molecular and electrophysiological association among NMDA and MDMA/Arachidonylcyclopropylamide (ACPA, a selective CB-1 receptor agonist) co-consumption was not well-known. Here, neuronal spontaneous activity, Brain-derived neurotrophic factor (BDNF), Trk-B and cAMP response element binding protein (CREB) phosphorylation levels were recognized in ACPA and MDMA co-injected rats. Besides, we proved the role of NMDA receptor on MDMA and ACPA combination on neuronal spontaneous activity and Trk-B/BDNF pathway in the central amygdala (CeA). Male rats were anesthetized with intra-peritoneal injections of urethane; MDMA, D-2-amino-5-phosphonopentanoate (D-AP5, NMDA receptor antagonist) were injected into CeA. ACPA was administrated by intra-cerebroventricular injection. Thirty minutes following injections, neuronal firing rate was recorded from CeA. Two hours after drug injection, amygdala was collected from brain for molecular evaluations. Single administration of MDMA and/or ACPA reduced firing rates compared with sham group in the CeA dose-dependently. Injection of D-AP5, ACPA and MDMA reduced firing rate compared with sham group (P<0.001). Interestingly, injection of ACPA+MDMA enhanced BDNF, Trk-B and CREB phosphorylation compared with MDMA groups. D-AP5, ACPA and MDMA co-injection decreased BDNF, Trk-B and CREB phosphorylation levels compared with ACPA+MDMA in the amygdala (P<0.01). Probably, NMDA receptors are involved in the protective role of acute MDMA+ACPA co-injection via BDNF/Trk-B/CREB pathways.

Graphical abstract

http://ift.tt/2l85AiW

Continuous ground-based aerosol Lidar observation during seasonal pollution events at Wuxi, China

Publication date: April 2017
Source:Atmospheric Environment, Volume 154
Author(s): Man Sing Wong, Kai Qin, Hong Lian, James R. Campbell, Kwon Ho Lee, Shijie Sheng
Haze pollution has long been a significant research topic and challenge in China, with adverse effects on air quality, agricultural production, as well as human health. In coupling with ground-based Lidar measurements, air quality observation, meteorological data, and backward trajectories model, two typical haze events at Wuxi, China are analyzed respectively, depicting summer and winter scenarios. Results indicate that the winter haze pollution is a compound pollution process mainly affected by calm winds that induce pollution accumulation near the surface. In the summer case, with the exception of influence from PM2.5 concentrations, ozone is the main pollutant and regional transport is also a significant influencing factor. Both events are marked by enhanced PM2.5 concentrations, driven by anthropogenic emissions of pollutants such as vehicle exhaust and factory fumes. Meteorological factors such as wind speed/direction and relative humidity are also contributed. These results indicate how the vertical profile offered by routine regional Lidar monitoring helps aid in understanding local variability and trends, which may be adapted for developing abatement strategies that improve air quality.



http://ift.tt/2kzje1K

Variations in particulate matter over Indo-Gangetic Plains and Indo-Himalayan Range during four field campaigns in winter monsoon and summer monsoon: Role of pollution pathways

Publication date: April 2017
Source:Atmospheric Environment, Volume 154
Author(s): A. Sen, A.S. Abdelmaksoud, Y. Nazeer Ahammed, Mansour ِA. Alghamdi, Tirthankar Banerjee, Mudasir Ahmad Bhat, A. Chatterjee, Anil K. Choudhuri, Trupti Das, Amit Dhir, Pitamber Prasad Dhyani, Ranu Gadi, Sanjay Ghosh, Kireet Kumar, A.H. Khan, M. Khoder, K. Maharaj Kumari, Jagdish Chandra Kuniyal, Manish Kumar, Anita Lakhani, Parth Sarathi Mahapatra, Manish Naja, Dharam Pal, S. Pal, Mahammad Rafiq, Shakil Ahmad Romshoo, Irfan Rashid, Prasenjit Saikia, D.M. Shenoy, Vijay Sridhar, Nidhi Verma, B.M. Vyas, Mohit Saxena, A. Sharma, S.K. Sharma, T.K. Mandal
Both in-situ and space-borne observations reveal an extremely high loading of particulates over the Indo-Gangetic Plains (IGP), all year around. With a burgeoning population and combustion sources (fossil fuels (FFs) and biofuels (BFs)) in close proximity to each other, the IGP is widely regarded as a hotspot for anthropogenic aerosol emission in South Asia. The deteriorating air quality over this region, particularly during winters, is a cause of major concern, since the pollutants undergo long range transport from their source regions to the Indo-Himalayan Range (IHR), Bay of Bengal (BoB) and other remote areas, polluting their pristine atmospheric conditions. Seasonal reversal in winds over the Indian mainland leads to an outflow of continental pollutants into the BoB during winters and a net advection of desert dust aerosols into the IGP from southwest Asia (SW-Asia), northwest India (NW-India) and northern Africa (N-Africa) during summers. Through the course of this study, four observational campaigns were conducted for sampling the ambient PM2.5 and PM10 during winter and summer seasons of 2014–2015, at multiple locations (18 sites) in the IGP, IHR, and semi-arid/arid sites towards their south and west, in order to accurately determine the inter-seasonal and inter-annual changes in the aerosol loading at the sites. We have also utilized data from Moderate Resolution Imaging Spectroradiometer (MODIS) on-board Earth Observing System (EOS) Terra satellite for estimating the columnar Aerosol Optical Depth at 550 nm (AOD550) and data from EOS Terra and Aqua satellites for discovering openly burning fires in the vicinity of sampling sites. Determination of the major source regions and key transport pathways during both seasons have also been attempted, using back-trajectory cluster analyses, as well as receptor models such as PSCF and CWT.



http://ift.tt/2jNUHSk

Greenhouse gases concentrations and fluxes from subtropical small reservoirs in relation with watershed urbanization

Publication date: April 2017
Source:Atmospheric Environment, Volume 154
Author(s): Xiaofeng Wang, Yixin He, Xingzhong Yuan, Huai Chen, Changhui Peng, Junsheng Yue, Qiaoyong Zhang, Yuanbin Diao, Shuangshuang Liu
Greenhouse gas (GHG) emissions from reservoirs and global urbanization have gained widespread attention, yet the response of GHG emissions to the watershed urbanization is poorly understood. Meanwhile, there are millions of small reservoirs worldwide that receive and accumulate high loads of anthropogenic carbon and nitrogen due to watershed urbanization and can therefore be hotspots of GHG emissions. In this study, we assessed the GHG concentrations and fluxes in sixteen small reservoirs draining urban, agricultural and forested watersheds over a period of one year. The concentrations of pCO2, CH4 and N2O in sampled urban reservoirs that received more sewage input were higher than those in agricultural reservoirs, and were 3, 7 and 10 times higher than those in reservoirs draining in forested areas, respectively. Accordingly, urban reservoirs had the highest estimated GHG flux rate. Regression analysis indicated that dissolved total phosphorus, dissolved organic carbon (DOC) and chlorophyll-a (Chl-a) had great effect on CO2 production, while the nitrogen (N) and phosphorus (P) content of surface water were closely related to CH4 and N2O production. Therefore, these parameters can act as good predictors of GHG emissions in urban watersheds. Given the rapid progress of global urbanization, small urban reservoirs play a crucial role in accounting for regional GHG emissions and cannot be ignored.



http://ift.tt/2kzthnL

Role of persistent low-level clouds in mitigating air quality impacts of wintertime cold pool conditions

Publication date: April 2017
Source:Atmospheric Environment, Volume 154
Author(s): Timothy M. VanReken, Ranil S. Dhammapala, B. Thomas Jobson, Courtney L. Bottenus, Graham S. VanderSchelden, Susan D. Kaspari, Zhongming Gao, Qiurui Zhu, Brian K. Lamb, Heping Liu, Jeff Johnston
The Yakima Air Wintertime Nitrate Study (YAWNS) was conducted in January 2013 to investigate the drivers of elevated levels of fine particulate matter (PM2.5) frequently present in the region during winter stagnation periods. An extended stagnation period occurred during the study. For the first four days of the event, skies were clear and the strong diel variation in air pollution patterns were consistent with the expected effects of strong low-level nighttime temperature inversions with moderate mixing during daylight hours. Later in the event a low-level cloud layer formed that persisted over the Yakima Valley for the next seven days while regional conditions remained stagnant. Coincident with the onset of cloud, the levels of all measured primary pollutants, including CO2, CO, NOx, particle number concentration, and black carbon, dropped dramatically and remained low with negligible diel variation for as long as the cloud layer was present. The observed patterns for these air pollutants are consistent with decreased stability and enhanced mixing associated with the cloud-topped boundary layer. Interestingly, levels of secondary pollutants, most notably particulate ammonium nitrate, did not exhibit the same decline. This difference may be due to shifts in the chemical production of secondary pollutants during cloudy conditions, or may merely reflect a further influence of mixing. The results imply that the best strategies for managing wintertime air quality during episodes of persistent cloud are likely different from those needed during clear-sky stagnation events.



http://ift.tt/2jNRUZ4

Studying partner violence to understand gender motivations - or vice-versa?

Publication date: Available online 4 February 2017
Source:Aggression and Violent Behavior
Author(s): Zeev Winstok, Michael Weinberg, Ronit Smadar-Dror
This article critically reviews the literature on gender differences in intimate partner violence. The review reveals that many researchers view partner violence as an opportunity to learn about gender. This approach is examined and its limitations are pointed out. A reverse approach is proposed which views the study of gender as an opportunity to learn about partner violence. This alternative approach identifies gender motives in general and moves on to explore the expressions of these motives in violent and non-violent intimate relationships. Theoretical and practical implications for this alternative approach are suggested. An important implication is the moderating effect of the proposed approach on the ongoing controversy over the role of gender in partner violence.



http://ift.tt/2jNSztN

Tashkeela: Novel corpus of Arabic vocalized texts, data for auto-diacritization systems

Publication date: Available online 3 February 2017
Source:Data in Brief
Author(s): Taha Zerrouki, Amar Balla
Arabic diacritics are often missed in Arabic scripts. This feature is a handicap for new learner to read َArabic, text to speech conversion systems, reading and semantic analysis of Arabic texts.The automatic diacritization systems are the best solution to handle this issue. But such automation needs resources as diactritized texts to train and evaluate such systems.In this paper, we describe our corpus of Arabic diacritized texts. This corpus is called Tashkeela. It can be used as a linguistic resource tool for natural language processing such as automatic diacritics systems, dis-ambiguity mechanism, features and data extraction.The corpus is freely available, it contains 75 million of fully vocalized words mainly 97 books from classical and modern Arabic language.The corpus is collected from manually vocalized texts using web crawling process.



http://ift.tt/2kDboDW

1H NMR spectra dataset and solid-state NMR data of cowpea (Vigna unguiculata)

Publication date: Available online 3 February 2017
Source:Data in Brief
Author(s): Elenilson G. Alves Filho, Lorena M.A. Silva, Elizita M. Teofilo, Flemming H. Larsen, Edy S. de Brito
In this article the NMR data from chemical shifts, coupling constants, and structures of all the characterized compounds were provided, beyond a complementary PCA evaluation for the corresponding manuscript (Elenilson G. Alves Filho, Silva, Teofilo, Larsen, & de Brito, 2017). In addition, a complementary assessment from solid-state NMR data was provided. For further chemometric analysis, numerical matrices from the raw ¹H NMR data were made available in Microsoft Excel workbook format (.xls).



http://ift.tt/2l7X6rQ

Dataset on the learning performance of ECDL digital skills of undergraduate students for comparing educational gaming, gamification and social networking

Publication date: Available online 3 February 2017
Source:Data in Brief
Author(s): Luis de-Marcos, Eva García-López, Antonio García-Cabot
This paper reports data about the learning performance of students using four different motivational tools: an educational game, a gamified plugin, a social networking website and a gamified social networking website. It also reports a control group. The data pertain to 379 students of an undergraduate course that covers basic Information and Communication Technology (ICT) skills in Spain. Data corresponds to different learning modules of the European Computer Driving License (ECDL) initiative. The data include variables of four pre-test scores, four post-test scores and a final examination. It was gathered using a quasi-experimental research design during 2014. Data reported here refers to the research paper in [1].



http://ift.tt/2kDcory

Fibronectin and androgen receptor expression data in prostate cancer obtained from a RNA-sequencing bioinformatics analysis

Publication date: Available online 3 February 2017
Source:Data in Brief
Author(s): Dibash K. Das, Thahmina Ali, Konstantinos Krampis, Olorunseun O. Ogunwobi
Prostate cancer is the second most commonly diagnosed male cancer in the world. The molecular mechanisms underlying its development and progression are still unclear. Here we show analysis of a prostate cancer RNA-sequencing dataset that was originally generated by Ren et al. [3] from the prostate tumor and adjacent normal tissues of 14 patients. The data presented here was analyzed using our RNA-sequencing bioinformatics analysis pipeline implemented on the bioinformatics web platform, Galaxy. The relative expression of fibronectin (FN1) and the androgen receptor (AR) were calculated in fragments per kilobase of transcript per million mapped reads, and represented in FPKM unit. A subanalysis is also shown for data from three patients, that includes the relative expression of FN1 and AR and their fold change. For interpretation and discussion, please refer to the article, "miR-1207-3p regulates the androgen receptor in prostate cancer via FNDC1/fibronectin" [1] by Das et al.



http://ift.tt/2l847sV

Photocatalytic oxidation of urea on TiO 2 in water and urine: mechanism, product distribution, and effect of surface platinization

Abstract

The photocatalytic oxidation of urea on TiO₂ in water was compared with that in urine. Despite the presence of other organic compounds in urine, the oxidation efficiency of urea on TiO₂ in urine was higher than that in water. This enhanced oxidation of urea in urine is ascribed to the higher production of ^•OH (primary oxidant for urea degradation) by the adsorption of PO₄³⁻ (one constituent of urine) on the TiO₂ surface. Among the various anions in urine, only PO₄³⁻ was adsorbed on the surface of TiO₂. Both the production of ^•OH and the oxidation of urea were enhanced in the presence of PO₄³⁻. These results indicate that the enhanced ^•OH production by in situ surface phosphorylation is the reason for the increased oxidation of urea in urine. Surface platinization of TiO₂ enhanced the oxidation of urea in water. However, the oxidation efficiency of urea on Pt/TiO₂ in urine was lower than that in water. This behavior is due to the adsorption of PO₄³⁻ and SO₄²⁻ in urine on Pt deposits, which inhibits the adsorption of oxygen and the interfacial electron transfer to oxygen. The product distribution (i.e., the molar ratio of NO₃⁻ to NH₄⁺) in water was different from that in urine because the negatively charged surface of TiO₂ in urine attracts the positively charged area of carbamic acid (intermediate) and encourages its decomposition into NH₄⁺ and not into NO₃⁻.

http://ift.tt/2l85Xdf

Health Promotion and Healthier Products Increase Vending Purchases: A Randomized Factorial Trial

Publication date: Available online 3 February 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Sophia V. Hua, Lisa Kimmel, Michael Van Emmenes, Rafi Taherian, Geraldine Remer, Adam Millman, Jeannette R. Ickovics
BackgroundThe current food environment has a high prevalence of nutrient-sparse foods and beverages, most starkly seen in vending machine offerings. There are currently few studies that explore different interventions that might lead to healthier vending machine purchases.ObjectiveTo examine how healthier product availability, price reductions, and/or promotional signs affect sales and revenue of snack and beverage vending machines.DesignA 2×2×2 factorial randomized controlled trial was conducted.Participants/settingStudents, staff, and employees on a university campus.InterventionAll co-located snack and beverage vending machines (n=56, 28 snack and 28 beverage) were randomized into one of eight conditions: availability of healthier products and/or 25% price reduction for healthier items and/or promotional signs on machines. Aggregate sales and revenue data for the 5-month study period (February to June 2015) were compared with data from the same months 1 year prior. Analyses were conducted July 2015.Main outcome measuresThe change in units sold and revenue between February through June 2014 and 2015.Statistical analyses performedLinear regression models (main effects and interaction effects) and t test analyses were performed.ResultsThe interaction between healthier product guidelines and promotional signs in snack vending machines documented increased revenue (P<0.05). Beverage machines randomized to meet healthier product guidelines documented increased units sold (P<0.05) with no revenue change. Price reductions alone had no effect, nor were there any effects for the three-way interaction of the factors. Examining top-selling products for all vending machines combined, pre- to postintervention, we found an overall shift to healthier purchasing.ConclusionsWhen healthier vending snacks are available, promotional signs are also important to ensure consumers purchase those items in greater amounts. Mitigating potential loss in profits is essential for sustainability of a healthier food environment.



http://ift.tt/2jKh9k6

The impact of contact on students’ attitudes towards peers with disabilities

Publication date: March 2017
Source:Research in Developmental Disabilities, Volume 62
Author(s): Susanne Schwab
This study aimed to understand the relationship between contact with peers with Special Educational Needs (SEN) and students' attitudes towards their peers with SEN, by examining the inter-group contact theory in regular and inclusive classes. A total of 463 students in 8th grade, with a mean age of 14.42 years, from 25 secondary school classes in Styria (Austria) completed a self-report questionnaire regarding their contact with peers with SEN and their attitudes towards peers with disabilities. Contact was indicated by nominations for joint activities and examined in inclusive and regular classes. The German short version of the Chedoke-McMaster Attitudes towards Children with Handicaps scale (CATCH; Schwab, 2015b; Rosenbaum et al., 1986) was used to measure students' attitudes towards peers with learning disabilities and emotional disorders. Students with SEN are less frequently nominated by their peers for joint activities, such as working together on a school project. Students from inclusive and regular classes did not differ in their attitudes towards peers with SEN. However, those students who nominated at least one peer with SEN for a joint activity had more positive attitudes towards peers with disabilities. Freely choosing contact with a peer with SEN was associated with more positive attitudes towards disability while simply attending the same class may have no effect or even a negative impact on students' attitudes.



http://ift.tt/2ks3OKm

Prosociality from early adolescence to young adulthood: A longitudinal study of individuals with a history of language impairment

Publication date: March 2017
Source:Research in Developmental Disabilities, Volume 62
Author(s): Umar Toseeb, Andrew Pickles, Kevin Durkin, Nicola Botting, Gina Conti-Ramsden
BackgroundLongitudinal research into the development of prosociality contributes vitally to understanding of individual differences in psychosocial outcomes. Most of the research to date has been concerned with prosocial behaviour in typically developing young people; much less has been directed to the course of development in individuals with developmental disorders.AimsThis study reports a longitudinal investigation of prosocial behaviour in young people with language impairment (LI), and compares trajectories of development to typically developing age-matched peers (AMPs).Methods and proceduresParticipants were followed from age 11 years to young adulthood (age 24 years).Outcomes and resultsParticipants with LI perceived themselves as prosocial; their ratings – though lower than those for the AMPs – were well within the normal range and they remained consistently so from 11 to 24 years. Two different developmental trajectories were identified for the LI group, which were stable and differed only in level of prosociality. Approximately one third of participants with LI followed a moderate prosociality trajectory whilst the majority (71%) followed a prosocial trajectory. We found evidence of protective effects of prosociality for social outcomes in young adulthood.Conclusions and implicationsThe findings indicate that prosociality is an area of relative strength in LI.What this paper adds?To our knowledge, this is the first study to examine developmental changes in levels of prosociality from early adolescence to young adulthood in a cohort of young people with LI. Approximately one third of participants with LI followed a moderate prosociality trajectory whilst the majority (71%) followed a prosocial trajectory. We argue that prosociality is different to other areas of functioning in LI. Prosociality appears to be an area of relative strength and can act as a protective factor in social functioning. Prosociality was associated with better community integration in young adulthood and was significantly protective against friendship difficulties for individuals with LI. This paper also raises the thought-provoking issue of potential distal effects of early identification and intensive support for LI. It is important to note that all of the participants with LI in this study had been identified as having language difficulties in childhood and had received intensive intervention for their difficulties in language units attached to mainstream schools across England. The early identification of language difficulties and the context of early, intensive language support received in educational contexts such as language units may have nurtured socialisation processes and the development of emphatic concern, which in turn influence the development of prosociality later in young adulthood. More individual differences in prosociality have been reported for other samples drawn from a variety of schools with different educational provision and levels of language support and younger age groups, such as primary school-aged children with LI.



http://ift.tt/2l3vuIm

Dietary reconstruction of the El Sidrón Neandertal familial group (Spain) in the context of other Neandertal and modern hunter-gatherer groups. A molar microwear texture analysis

Publication date: March 2017
Source:Journal of Human Evolution, Volume 104
Author(s): Almudena Estalrrich, Sireen El Zaatari, Antonio Rosas
Here, we present the analysis of occlusal molar microwear textures of eight individuals from the El Sidrón Neandertal group (Spain). The aims of the study were: 1) to document potential age-, sex-, and maternal lineage-related differences in diet within a Neandertal familial group, and 2) to place the diet of El Sidrón individuals in the context of those of other Neandertal groups. This study also offers an interpretation of the diet of the El Sidrón Neandertals by comparing their microwear signatures to those of recent hunter-gatherer populations with diverse but known diets. The intra-group examination of the microwear signatures are consistent with the females of the El Sidrón group having had more abrasive diets or having used their teeth in more para-masticatory activities than did the males. Aside from the potential sex-related differences in diet, no additional intra-group dietary separation, such as by age group or maternal lineage, was observed. In comparison to other Neandertals, El Sidrón individuals, as a group, have microwear signatures most similar to those of other Neandertals from wooded habitats and different from those that lived in more open habitats. This result is expected based on the available paleoenvironmental reconstructions from El Sidrón Cave. The diet of the El Sidrón Neandertals, just like their Neandertal counterparts from similar wooded habitats, is interpreted as having been mixed, consisting of both meat and vegetable foods.



http://ift.tt/2kDcvU1

Adaptation to suspensory locomotion in Australopithecus sediba

Publication date: March 2017
Source:Journal of Human Evolution, Volume 104
Author(s): Thomas R. Rein, Terry Harrison, Kristian J. Carlson, Katerina Harvati
Australopithecus sediba is represented by well-preserved fossilized remains from the locality of Malapa, South Africa. Recent work has shown that the combination of features in the limb skeleton of A. sediba was distinct from that of earlier species of Australopithecus, perhaps indicating that this species moved differently. The bones of the arm and forearm indicate that A. sediba was adapted to suspensory and climbing behaviors. We used a geometric morphometric approach to examine ulnar shape, potentially identifying adaptations to forelimb suspensory locomotion in A. sediba. Results indicated suspensory capabilities in this species and a stronger forelimb suspensory signal than has been documented in Australopithecus afarensis. Our study confirms the adaptive significance of functional morphological traits for arboreal movements in the locomotor repertoire of A. sediba and provides important insight into the diversity and mosaic nature of locomotor adaptations among early hominins.



http://ift.tt/2l80ZwZ

Editorial Board

Publication date: February 2017
Source:Journal of Human Evolution, Volume 103





http://ift.tt/2l7NxcG

Global Adverse Event Reports of Breast Implant-Associated ALCL: An International Review of 40 Government Authority Databases.

Background: An estimated 200 patients have been reported with breast implant associated anaplastic large cell lymphoma (BI-ALCL), a rare T-cell lymphoma developing around breast prostheses. The purpose of this study was to review federal database submissions relating to BI-ALCL in 37 countries representing the majority of breast implant markets worldwide with available adverse event reporting. Methods: Database queries were performed for Australia, Brazil, Canada, China, Columbia, Japan, Mexico, National Competent Authorities of the European Member States, New Zealand, South Korea, and United States. Demographics, device characteristics, pathology, treatment modalities, and outcomes were assessed when available. Results: The United States MAUDE database included 459 entries in total for the search terms "Anaplastic" and "ALCL" as of September 2015. Excluding for duplicate entries, the MAUDE database had 258 unique cases of BI-ALCL of which 130 had pathologic markers performed. Implant surface was textured significantly more than smooth (50% vs. 4.2%, p=0.0001). Treatment, when reported (n=136), included explantation (n=125, 91.9%), chemotherapy (n=42, 30.8%), radiation (n=25, 18.4%), and/or stem cell transplant (n=9, 6.6%) and 5 deaths were reported. For the 40 countries queried, 340 unique cases were reported for lymphoma associated with breast implants. Conclusions: Worldwide federal reporting of BI-ALCL has significant limitations in providing data regarding clinical history, treatment, and oncologic follow up. Country-specific total implant and textured implant sales data is needed in order to determine critical incidence and prevalence analysis. Detailed BI-ALCL patient registries such as American Society of Plastic Surgeon's PROFILE and centralized tissue banking are necessary in acquiring accurate complete data for sound decision making. (C)2017American Society of Plastic Surgeons

http://ift.tt/2kzll5P

United States Epidemiology of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Background: Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a distinctive type of T-cell lymphoma that arises around breast implants. Although rare, all cases of BI-ALCL with adequate history have involved a textured breast implant. The objective of this study is to determine the United States incidence and lifetime prevalence of BI-ALCL in women with textured breast implants. Methods: This is a retrospective review of documented cases of BI-ALCL in the United States from 1996 to 2015. The incidence and prevalence of BI-ALCL was determined based on a literature and institutional database review of BI-ALCL cases and textured breast implant sales figures from implant manufacturers' annualized data. Results: One hundred pathologically confirmed BI-ALCL cases were identified in the United States. Mean age at diagnosis was 53.2+/-12.3 years. Mean interval from implant placement to diagnosis was 10.7+/-4.6 years. Forty-nine patients had breast implants placed for cosmetic reasons, 44 for mastectomy reconstruction, and 7 for unknown reasons. Assuming BI-ALCL occurs only in textured breast implants, the incidence rate is 2.03 per 1,000,000 person-years (203 per 100 million), which is 67.6 times higher than that of breast ALCL (3 per 100 million; p

http://ift.tt/2jNM2za

Malignancy rates in a large cohort of patients with systemically treated psoriasis in a managed care population

Publication date: Available online 3 February 2017
Source:Journal of the American Academy of Dermatology
Author(s): Maryam M. Asgari, G. Thomas Ray, Jamie L. Geier, Charles P. Quesenberry
BackgroundModerate to severe psoriasis often requires treatment with systemic agents, many of which have immunosuppressive properties and could increase cancer risk, including nonmelanoma skin cancer (NMSC).ObjectiveWe sought to estimate the overall malignancy rate (excluding NMSC) and NMSC rate among 5889 patients with systemically treated psoriasis.MethodsWe identified a cohort of adult Kaiser Permanente Northern California health plan members with psoriasis diagnosed from 1998 to 2011 and treated with at least 1 systemic antipsoriatic agent and categorized them into ever-biologic or nonbiologic users. Malignancy rates were calculated per 1000 person-years of follow-up with 95% confidence intervals (CI). Crude and confounder-adjusted hazard ratios (aHRs) were calculated using Cox regression.ResultsMost biologic-exposed members were treated with TNF-alfa inhibitors (n = 2214, 97%). Overall incident cancer rates were comparable between ever-biologic as compared to nonbiologic users (aHR 0.86, 95% CI 0.66-1.13). NMSC rates were 42% higher among individuals ever exposed to a biologic (aHR 1.42, 95% CI 1.12-1.80), largely driven by increased cutaneous squamous cell carcinoma risk (aHR 1.81, 95% CI 1.23-2.67).LimitationsNo information was available on disease severity.ConclusionWe found increased incidence of cutaneous squamous cell carcinoma among patients with systemically treated psoriasis who were ever exposed to biologics, the majority of which were TNF-alfa inhibitors. Increased skin cancer surveillance in this population may be warranted.



http://ift.tt/2jKaSF7

The role of immunosuppression in squamous cell carcinomas arising in seborrheic keratosis

Publication date: Available online 3 February 2017
Source:Journal of the American Academy of Dermatology
Author(s): Ruzica Z. Conic, Karl Napekoski, Heidi Schuetz, Melissa Piliang, Wilma Bergfeld, Natasha Atanaskova Mesinkovska
BackgroundSeborrheic keratoses (SK) are common skin neoplasms considered to be benign. Reports of associated squamous cell carcinoma arising within seborrheic keratosis (SCC-SK) have been described.ObjectiveTo describe the histopathologic characteristics of SCC-SK and identify predisposing factors in formation of these rare lesions.MethodsThere were 162 cases of SCC-SK in a span of a decade (2003-2014). All of the histopathologic specimens and medical records were reviewed. Data from these patients were compared to a control group with seborrheic keratosis who were matched by age, sex, and location of lesion from the same time period (n = 162).ResultsSCC-SK has the classic histopathologic features of SK, such as hyperkeratosis, parakeratosis, papillomatosis, and pseudohorn cysts. The areas of squamous cell carcinoma were characterized by areas of squamous dysplasia (100%), hypogranulosis (79.6%), squamous eddies (79.6%), solar elastosis (80.9%), and brown pigmentation (59.9%).Patients with a history of immunosuppression had an increased risk for developing SCC-SK (19% vs 3%; P < .01), particularly when inhibition was transplant-associated (10% vs 0%; P < .01).LimitationsThis was a single center, retrospective study.ConclusionSCC-SK occurs more often in elderly men with a history of immunosuppression associated with organ transplants.



http://ift.tt/2k6IVU3

Efficacy of iontophoresis-assisted ablative fractional laser photodynamic therapy with short incubation time for the treatment of actinic keratosis: 12-month follow-up results of a prospective, randomised, comparative trial

Publication date: Available online 3 February 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Seung-Hwan Choi, Tae-Hoon Kim, Ki-Hoon Song
BackgroundIontophoresis is a transdermal drug-delivery technique that enhances the transport of ionic species across membranes and may have significant benefit for the treatment of actinic keratosis (AK) by ablative fractional laser–primed photodynamic therapy (AFL-PDT). The aim of this study were to compare the efficacy, recurrence rate, cosmetic outcome and safety of iontophoresis-assisted AFL-PDT with 2hours of incubation vs. those of conventional AFL-PDT with 2- and 3-hour incubation in patients with facial and scalp AK.MethodsPatients were randomly assigned to iontophoresis-assisted AFL-PDT with a 2-hour incubation time (group A) and conventional AFL-PDT with a 2-hour (group B) and 3-hour (groupC) incubation time. All patients underwent AFL-PDT, and group A patients were assigned to treatment with iontophoresis after methyl-aminolevulinate (MAL) application. After 2 or 3hours, MAL-applied lesions were irradiated using a red light. Patients were followed up at 1 week, 3 months and 12 months after treatment. Efficacy, cosmetic outcomes and adverse events were assessed.ResultsIn total, 41 patients (160 AK lesions) completed the study and were evaluated. Efficacy was significantly higher in Group A (88.7%) than in Group B (73.2%); the efficacy of groups A and C (92.2%) at 3 months follow-up was comparable. The recurrence rates were not significantly different between the groups at 12 months (P=0.841). The three groups did not differ in terms of cosmetic outcomes and safety.ConclusionsIontophoresis-assisted AFL-PDT showed higher efficacy than AFL-PDT with short incubation time. Iontophoresis may effectively reduce the incubation time in AFL-PDT.



http://ift.tt/2krKsF3

Solid-phase extraction microfluidic devices for matrix removal in trace element assay of actinide materials

Publication date: 15 May 2017
Source:Talanta, Volume 167
Author(s): Jun Gao, Benjamin T. Manard, Alonso Castro, Dennis P. Montoya, Ning Xu, Rebecca M. Chamberlin
Advances in sample nebulization and injection technology have significantly reduced the volume of solution required for trace impurity analysis in plutonium and uranium materials. Correspondingly, we have designed and tested a novel chip-based microfluidic platform, containing a 100-µL or 20-µL solid-phase microextraction column, packed by centrifugation, which supports nuclear material mass and solution volume reductions of 90% or more compared to standard methods. Quantitative recovery of 28 trace elements in uranium was demonstrated using a UTEVA chromatographic resin column, and trace element recovery from thorium (a surrogate for plutonium) was similarly demonstrated using anion exchange resin AG MP-1. Of nine materials tested, compatibility of polyvinyl chloride (PVC), polypropylene (PP), and polytetrafluoroethylene (PTFE) chips with the strong nitric acid media was highest. The microcolumns can be incorporated into a variety of devices and systems, and can be loaded with other solid-phase resins for trace element assay in high-purity metals.

Graphical abstract

http://ift.tt/2l7NgGu

ELIME assay vs Real-Time PCR and conventional culture method for an effective detection of Salmonella in fresh leafy green vegetables

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): L. Fabiani, E. Pucci, E. Delibato, G. Volpe, S. Piermarini, D. De Medici, F. Capuano, G. Palleschi
The detection of Salmonella according to EC regulation is still primarily based on traditional microbiological culture methods that may take several days to be completed.The purpose of this work is to demonstrate the applicability of an Enzyme-Linked-Immuno-Magnetic-Electrochemical (ELIME) assay, recently developed by our research group for the detection of salmonella in irrigation water, in fresh (raw and ready-to-eat) leafy green vegetables by comparison with Real-Time PCR (RTi-PCR) and ISO culture methods.Since vegetables represent a more complex matrix than irrigation water, preliminary experiments were carried out on two leafy green vegetables that resulted negative for salmonella by the ISO method. 25g of these samples were experimentally inoculated with 1–10 CFU of S. Napoli or S. Thompson and pre-enriched for 20h in two different broths. At this time aliquots were taken, concentrated at different levels by centrifugation, and analyzed by ELIME and RTi-PCR. Once selected the best culture medium for salmonella growth, and the optimal concentration factor suitable to reduce the sample matrix effect, enhancing the out-put signal, several raw and ready-to-eat leafy green vegetables were artificially inoculated and pre-enriched. Aliquots were then taken at different incubation times and analyzed with both techniques. Results obtained showed that 20 and 8h of pre-enrichment were required to allow the target salmonella (1–10 CFU/25g) to multiply until reaching a detectable concentration by ELIME and RTi-PCR assays, respectively. A confirmation with the ISO culture method was carried out. Based on the available literature, this is the first report of the application of an ELISA based method for the detection of Salmonella in vegetables.

Graphical abstract

http://ift.tt/2l7XDKs

Determination of Pd(II) using an antimony film coated on a screen-printed electrode by adsorptive stripping voltammetry

Publication date: 15 May 2017
Source:Talanta, Volume 167
Author(s): Clara Pérez-Ràfols, Pedro Trechera, Núria Serrano, José Manuel Díaz-Cruz, Cristina Ariño, Miquel Esteban
The use of an antimony film coated on a screen-printed carbon electrode (ex-situ SbSPCE) is proposed for the determination of Pd(II) at ppb levels in natural samples by adsorptive stripping voltammetry using dimethylglyoxime as chelating agent. Ex-situ SbSPCE produces a better analytical performance as compared to a commercially sputtered bismuth screen-printed electrode (BispSPE). The detection and quantification limits were 2.7 and 9.0µgL⁻¹ respectively with a good linear behaviour in the wide examined concentration range (from 1µgL⁻¹ up to 100.0µgL⁻¹, R²=0.998). The proposed ex-situ SbSPCE showed an excellent repeatability with a relative standard deviation of 0.5% for ten successive measurements and a very good reproducibility (1.6% for three different ex-situ SbSPCE units within series of ten repetitive assays). Moreover, the ex-situ SbSPCE was successfully applied for the determination of low concentration levels of Pd(II) in spiked tap water with a very high reproducibility (0.2%) and providing equivalent results to those achieved by ICP-MS measurements.

Graphical abstract

http://ift.tt/2l7V9fd

Multi-residue analysis of 36 priority and emerging pollutants in marine echinoderms (Holothuria tubulosa) and marine sediments by solid-liquid extraction followed by dispersive solid phase extraction and liquid chromatography–tandem mass spectrometry analysis

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): J. Martín, A. Zafra-Gómez, F. Hidalgo, A.J. Ibáñez-Yuste, E. Alonso, J.L. Vilchez
Marine echinoderms are filter-feeding invertebrates widely distributed along the coasts, and which are therefore extensively exposed to anthropogenic xenobiotics. They can serve as good sentinels for monitoring a large variety of contaminants in marine ecosystems. In this context, a multi-residue analytical method has been validated and applied to Holothuria tubulosa specimens and marine sediments for the determination of 36 organic compounds, which belong to some of the most problematic groups of emerging and priority pollutants (perfluoroalkyl compounds, estrogens, parabens, benzophenones, plasticizers, surfactants, brominated flame retardants and alkylphenols). Lyophilization of samples prior to solvent extraction and clean-up of extracts with C18, followed by liquid chromatography–tandem mass spectrometry analysis, is proposed. A Box–Behnken design was used for optimization of the most influential variables affecting the extraction and clean-up steps. For validation, matrix-matched calibration and recovery assay were applied. Linearity (% r²) higher than 99%, recoveries between 80% and 114% (except in LAS and NP1EO), RSD (precision) lower than 15% and limits of quantification between 0.03 and 12.5ngg⁻¹ dry weight (d.w.) were achieved. The method was applied to nine samples of Holothuria collected along the coast of Granada (Spain), and to marine sediments around the animals. The results demonstrated high bioaccumulation of certain pollutants. A total of 25 out of the 36 studied compounds were quantified, being surfactants, alkylphenols, perfluoroalkyl compounds, triclocarban and parabens the most frequently detected. Nonylphenol was found in the highest concentration (340 and 323ngg⁻¹ d.w. in sediment and Holothuria samples, respectively).

Graphical abstract

http://ift.tt/2l88lRb

Sensitive and precise monitoring of phosphatidylethanol in human blood as a biomarker for alcohol intake by ultrasound-assisted dispersive liquid-liquid microextraction combined with liquid chromatography tandem mass spectrometry

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): Siming Wang, Ruiyue Yang, Fusui Ji, Hongxia Li, Jun Dong, Wenxiang Chen
Phosphatidylethanol (PEth) is a special phospholipid that is only formed in the presence of ethanol, and therefore, serves as a promising biomarker for alcohol intake. In this study, a simple, rapid and precise method based on LC-MS/MS combined with ultrasound-assisted dispersive liquid-liquid microextraction was developed and validated for the measurements of PEth (16:0/18:1, 16:0/18:2, 16:0/16:0, and 18:1/18:1) in human blood. The influences of several variables for sample extraction and MS detection were carefully investigated. The extraction efficiencies for all the four PEth species were markedly increased compared with the traditional extractions. A limit of detection below 0.56ngmL⁻¹ was obtained. This high sensitivity makes it possible to monitor various alcohol consumption levels in light to heavy drinkers. Good linearity was obtained for all the analytes without interference from the sample matrix. The imprecisions of the intra-run and total assays were lower than 3.1% and 6.5%, respectively, with an average recovery of 99.87%. In addition, the utility of the method was evaluated in an alcohol intake status study. The results indicate that the developed protocol is simple, precise, and sensitive, and can be easily adapted for objective and reliable assessments of alcohol intake in clinical research.

Graphical abstract

http://ift.tt/2l81cQJ

Cocaine profiling: Implementation of a predictive model by ATR-FTIR coupled with chemometrics in forensic chemistry

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): Stefano Materazzi, Adolfo Gregori, Luigi Ripani, Azzurra Apriceno, Roberta Risoluti
In this study, a strategy based on Infrared Spectroscopy with Fourier Transformed and Attenuated Total Reflectance associated with chemometrics (ATR-FTIR) is proposed to identify the chemical "fingerprint" of cocaine samples. To this end, standard mixtures of cocaine and cuttings at differents ratio were investigated in order to develop a multivariate classification model to simultaneously predict the composition of the samples and to obtain a profile of adulteration of cocaine seizures. In addition, the application of a Partial Least Squares (PLS) and Principal Component Regression (PCR) calibration approaches were found to be a useful tool to predict the content of cocaine, caffeine, procaine, lidocaine and phenacetin in drug seizures. The achieved results on real confiscated samples, in cooperation with the Italian Scientific Investigation Department (Carabinieri-RIS) of Rome, allow to consider ATR-FTIR followed to chemometrics as a promising forensic tool in such situations involving profile comparisons and supporting forensic investigations.

Graphical abstract

http://ift.tt/2l7TZQD

Zosteriform Mycosis Fungoides: A New Clinical Presentation With a Dermatomal Distribution.

Classic mycosis fungoides (MF) presents with patches and plaques on the trunk and proximal extremities. However, numerous clinicopathologic variants have been described, making diagnosis challenging. Here, the authors report a 21-year-old woman with immunophenotypically and molecularly confirmed MF occurring in a dermatomal distribution. Awareness of this and other rare variants of MF is critical to avoid misdiagnosis. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2jNFvUZ

A Persistent Plantar Wart Treated With a 532-nm Potassium Titanyl Phosphate Laser.

No abstract available

http://ift.tt/2kCXKkf

Successful Treatment of Classic Kaposi Sarcoma With Long-Pulse Neodymium-Doped Yttrium Aluminum Garnet (Nd: YAG) Laser: A Preliminary Study.

BACKGROUND: Kaposi sarcoma (KS) is a systemic disease that can present with cutaneous lesions with or without internal involvement, mostly caused by infection with human herpesvirus-8. The treatment options include surgical excision, cryotherapy, radiotherapy, intralesional chemotherapy, laser, and elastic stockings for the prevention of lymphedema. OBJECTIVE: This article presents 7 cases with classic KS treated with the long-pulse neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. METHODS: Forty-nine lesions of 7 KS patients (5 stage 1, 2 stage 2A) were treated with Nd:YAG laser with a spot size of 4 to 6 mm and a fluence of 180 J/cm2 increased by 10 J/cm2 in the neighboring area to a maximum of 260 J/cm2. The pulse sequencing was 1.5, and delay time was 5 milliseconds. Sessions were continued at 4-week intervals for 2 to 4 sessions. RESULTS: All patients exhibited clinical and histological improvement. One session was sufficient for small lesions, whereas coalescing and multicentric lesions required up to 4 sessions. All the lesions healed in 2 to 4 weeks, with the only complication being mild atrophic scars. CONCLUSION: With the advantage of penetrating into deeper sites than other lasers, long-pulse Nd:YAG is an efficient and safe local treatment alternative especially for papulonodular and deeper lesions located on bony structures. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2l7UuKH

Superficial Electrosurgery: To Numb or Not to Numb?.

No abstract available

http://ift.tt/2kCWw8z

Successful Treatment of Under-Eye Pigmentation in Skin Type IV With a Picosecond Alexandrite Laser With Diffractive Lens Array.

No abstract available

http://ift.tt/2l7KjGa

Squamous Cell Carcinoma of the Lip-A Review of Squamous Cell Carcinogenesis of the Mucosal and Cutaneous Junction.

BACKGROUND: The lip is an anatomic junction for 2 disparate groups of cancer. Cutaneous squamous cell carcinoma (cSCC) is a common malignancy with a favorable prognosis, whereas oral-mucosal squamous cell carcinoma (omSCC) is associated with significantly higher rates of nodal disease and worse outcomes. The squamous cell carcinoma of the lip (lip SCC) is more aggressive than cSCC but less aggressive than omSCC. However, work-up and treatment vary between specialties. OBJECTIVES: The authors sought to review and compare the risk factors and clinical behavior of cSCC, omSCC, and lip SCC, review tumor biology of squamous cell carcinoma, and compare work-up and treatment algorithms for lip SCC. METHODS: A comprehensive PubMed and MEDLINE database search was performed with comparison of primary literature on cSCC, omSCC, and lip SCC. RESULTS: Lip SCC exhibits rates of nodal metastasis and death that are intermediate between cSCC and omSCC, and shares many similar biologic mechanisms. There are variations in the treatment guidelines between dermatology and otolaryngology for lip SCC. CONCLUSION: Lip SCC is an overlapping entity that poses many challenges to clinicians. Specialists should be aware of current staging modalities as well as imaging and treatment recommendations to optimize patient outcomes. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2kCR3yy

Safety and Effectiveness of VYC-15L, a Hyaluronic Acid Filler for Lip and Perioral Enhancement: One-Year Results From a Randomized, Controlled Study.

BACKGROUND: VYC-15L (Juvederm Volbella XC) is a nonanimal crosslinked hyaluronic acid (HA) gel with lidocaine. OBJECTIVE: To evaluate the safety and effectiveness of VYC-15L for lip and perioral enhancement versus a nonanimal stabilized HA with lidocaine (Restylane-L; NASHA). METHODS: This prospective multicenter study randomized 225 adults with minimal, mild, or moderate lip fullness on the validated 5-point Allergan Lip Fullness Scale (LFS) to treatment with VYC-15L or NASHA; optional touch-up was administered 30 days later. Subjects were followed for 1 year. The primary effectiveness end point was noninferiority of VYC-15L versus NASHA by mean change in LFS score from baseline to Month 3. RESULTS: The primary end point was met. At Month 3, LFS responder rates were 80.3% for VYC-15L versus 70.8% for NASHA. LFS responder rates exceeded 60% through 1 year with VYC-15L. Perioral lines severity improved for 65.4% and 66.2% of VYC-15L subjects at Month 3 and Year 1, respectively. At Month 3, 96.1% and 88.2% of subjects reported improvement in FACE-Q Satisfaction With Lips and Satisfaction With Lip Lines, respectively. Severe injection site responses were reported less frequently with VYC-15L than NASHA. CONCLUSION: VYC-15L was safe and effective for lip and perioral enhancement, with treatment effects lasting through 1 year. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2l7Q9XP